Synthesis germacranolides

The intramolecular Hiyama reaction is excellently suited for the construction of carbocyclic and heterocyclic ring systems of different size. In most examples, problems of induced diastereoselectivity are involved (Sections 1.3.3.3.9.2.2. and D.2.3.). In the total synthesis of the antitumor germacranolide ( )-costunolide from ( ,.E)-farnesol, the correctly substituted ( , )-cyclodecadiene moiety was constructed by an intramolecular Hiyama reaction22. 

Elephantopus mollis is interesting because it elaborates a series of cytotoxic antitumor germacranolides including molephantinin and phantomolin, which are cytotoxic in vitro and in vivo against Ehrlich ascites carcinoma and Walker 256 carcinosarcoma in rodents (104,105). Molephantinin mitigates DNA and protein synthesis in Ehrlich ascites carcinoma cells and DNA synthesis. What is the activity of molephantinin on apoptosis (106)1... 

Transannular cyclizations of cyclodecadiene monoepoxides have been studied in exhaustive detail, particularly amongst natural germacranolides, because of their relevance to biogenetic models for the synthesis of eudesmane- and guaiane-type sesquiterpenes. " A full discussion of this topic is beyond the scope of this chapter, but the examples collected in equations (54-64) provide the reader with an in-... 

The structural elucidation and total synthesis of sesquiterpenoid lactones such as the germacranolides [cf. (310)] and eudesmanolides [cf. (311)] continues to be a very... 

Pennanen has disclosed a further use of the a-epoxyketone-ynamine route to 2-furanones, this time in the synthesis of (+)-eremophilenolide. Other reports in the natural product area have included the photochemical synthesis of an optically active isomer of the germacranolide isoaritolactone, and the construction of the cardenolide side-chain. The readily available >-ribonolac-tone derivatives (135) have been converted into cyclic orthoformates, which on heating for several hours lead to the optically active butenolides (136) (Scheme 77) 256 Yields are good for three examples other methods for the conversion... 

An olehn metathesis reaction has been effected by photochemical [2 + 2] cycloaddition followed by thermolysis of the cyclobutane (Scheme 17). Thus thermolysis of the tricyclic c ,a ft,c/5-adduct (57) gave the cyclodeca-1,5-diene skeleton (58) present in germacranolides (Scheme 17). A closely related process is the [4C + 2C] annelation which has been utilized in the synthesis of lO-epi-juneol (61) (Scheme 18). The photoadduct (59) from piperitone and methyl cyclobutene-1-carboxylate was converted in four steps into the tricyclic compound (60). The strained tr-bond in (60) was cleaved with lithium naphthalide to give 10-epi-juneoI (61). ... 

Marshall JA, Lebreton J, DeHoff BS, Jenson TM. Total synthesis of the germacranolide ( )-aristolactone via [2,3]-Wit-tig ring contraction. Tetrahedron Lett. 1987 28(7) 723-726. 

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